It is well known that stored blood has for many years been quite effective in saving lives. Of course, difficulties in storing blood samples and blood components limit the use of stored blood.
A major problem with storing blood is the tendency for blood to coagulate after removal from a patient. For this reason, anticoagulant agents are added to blood immediately after its removal from a patient or a donor. The anticoagulants include more heparin, an antithrombin III cofactor and chelating agents such as trisodium citrate. While these agents have been generally effective, they each present disadvantages. For example, anticoagulants including heparin and citrate allow deteriorization of sensitive blood components, especially plasma clotting factors.
Heparin, of course, remains in the blood of a patient into which it has been infused, and may therefore increase the risk of bleeding until sufficient metabolism of heparin has occurred. Citrate is minimally toxic in high concentration and is readily metabolised by the liver into lactic acid which is then excreted. Therefore, in most cases, citrated blood or plasma is safe for infusion. However, in patients with significant liver damage, or where large amounts of citrated blood are rapidly infused, the patient may be unable to convert citrate to lactic acid at a sufficient rate and indeed death may result. Additionally, citrated blood containing added glucose may precipitate hyperglycemic shock in patients with glucose intolerance.
A large number of transfusions are performed under emergency conditions. During an emergency, hospital staff may be unable to determine whether the patient has a glucose intolerance or liver dysfunction prior to the time when transfusion must be performed. Accordingly, a strong need exists for a method which preserves blood in a form which can safely be infused into almost any patient.
The ability of normal saline to progressively prolong the coagulation time in vitro when added to blood in increasing amounts was first described by Copley and Houlihan in 1944 (Science 100: 505, 1944). Later they employed saline dilution of blood in a ratio of 1 part blood to 9 parts saline or 1 part blood to 14 parts saline to render the blood incoagulable. Paradoxically, Toscantins et al found that dilution of blood or plasma increased the rate of coagulation (Blood 6: 720-39, 1951). The biphasic effect of dilution of blood with saline was confirmed by Heather et al who demonstrated maximal coagulability at between 75 and 85 percent blood concentration with decreased coagulability at 70 percent blood concentration (British Journal of Surgery 67: 63-65, 1980). Current practices in surgery on the heart include hemodilution with cystalloid solutions to moderate levels (hematocrit of 30) and to extreme levels (hematocrit to 18).
While, as set forth above, it has been previously recognized that ultrahemodilution with isotonic saline can prevent coagulation, there have been no reports concerning the viability of ultrahemodiluted blood. Additionally, since storage space is increased by ultrahemodilution, there has been little incentive for those skilled in the art to conduct further research along these lines.
Moreover, ultrahemodiluted blood has sufficient oxygen carrying capacity to support homeostasis. There has been no prior recognition that ultrahemodiluted blood could be simply and inexpensively separated and concentrated back to a normal concentration capable of supporting homeostasis. Although, minimally diluted blood has been passed through heart-lung machines, the diluted blood remained capable of supporting homeostasis since the degree of blood dilution was within normal biological limits.
As the capacity of ultrafiltration is a function of the degree of hemodilution, the number of filters, and the filtration rate, the permissible degree of hemodilution cannot specifically be set forth.
Also, blood drawn from a patient often needs to be analyzed in a clinical laboratory for various purposes. Under all circumstances, it is desirable to minimize the actual amount of blood drawn. Nevertheless, accurately handling and transferring extremely minute amounts of liquid accurately can be difficult and expensive. Further, for increased accuracy, more than one sample per test or measurement is preferred.